Irritability In Children Research Articles

Severe irritability in children and teens: A new understanding

Severe irritability in children and teens: A new understanding

A symptom-level perspective on irritability, PTSD, and depression in children and adults

BackgroundAlthough irritability is a prominent clinical manifestation among traumatized populations, its relationships with other psychopathologies are rarely studied. Adopting a symptom-level perspective, this study aimed to explore how symptoms of irritability, posttraumatic stress disorder (PTSD), and depression are associated. MethodThe Brief Irritability Test, the PTSD Checklist for DSM-5, and the Patient Health Questionnaire-9 were used to measure irritability, PTSD, and depression, respectively, in a large sample of trauma-exposed children and adolescents (n = 5454), trauma-exposed adults (n = 4718), and children and adolescents with probable PTSD (n = 556). Exploratory graph analysis (EGA) and network analysis were conducted to examine potential communities and significant relations. ResultsAlthough irritability, PTSD, and depression were highly correlated at the disorder level, EGA results indicated that, at the symptom level, they formed highly stable and dense communities, respectively. Relations across disorders mainly emerged at symptoms related to negative cognition, dysphoria, and suicidal thoughts. Especially, strong transdiagnostic relations across all samples were “negative beliefs” and “suicidal thoughts”, “numbing” and “suicidal thoughts”, “startle” and “moving slowly or restless”, “bothering” and “moving slowly or restless”. Furthermore, irritability symptoms seem more central than PTSD and depression symptoms, with “snap” being the most central node across all networks, especially in the child and adolescent sample. ConclusionIrritability, PTSD, and depression are relatively independent constructs when analyzed at the symptom level. Irritability symptoms emerged as core symptoms in trauma-exposed populations. Our findings highlight the importance of independent assessment of irritability in the diagnosis and treatment of PTSD.

Concurrent and longitudinal neurostructural correlates of irritability in children

Irritability, or an increased proneness to frustration and anger, is common in youth; however, few studies have examined neurostructural correlates of irritability in children. The purpose of the current study was to examine concurrent and longitudinal associations between brain structure and irritability in a large sample of 9–10-year-old children. Participants included 10,647 children from the Adolescent Brain Cognitive Developmentsm Study (ABCD Study®). We related a latent irritability factor to gray matter volume, cortical thickness, and surface area in 68 cortical regions and to gray matter volume in 19 subcortical regions using structural equation modeling. Multiple comparisons were adjusted for using the false discovery rate (FDR). After controlling for age, sex, race/ethnicity, scanner model, parent’s highest level of education, medication use, and total intracranial volume, irritability was associated with smaller volumes in primarily temporal and parietal regions at baseline. Longitudinal analyses showed that baseline gray matter volume did not predict irritability symptoms at the 3rd-year follow-up. No significant associations were found for cortical thickness or surface area. The current study demonstrates inverse associations between irritability and volume in regions implicated in emotional processing/social cognition, attention allocation, and movement/perception. We advance prior research by demonstrating that neurostructural differences associated with irritability are already apparent by age 9–10 years, extending this work to children and supporting theories positing socioemotional deficits as a key feature of irritability.

Association of Irritability with Restricted, Repetitive Behaviors and Social Communication Challenges in Autistic Youth.

Although affective irritability is a common and concerning problem for autistic youth, limited research has examined relations among core autism characteristics and irritability. Therefore, this study investigated potential associations among types of restricted/repetitive behaviors (RRBs) and social communication challenges and irritability in autistic children and adolescents. Participants were 107 autistic youth recruited from a university-based autism clinical research program. Two hierarchical multiple regressions were conducted with Affective Reactivity Index as the dependent variable. Covariates were entered at step 1, followed by the independent variables of interest at step 2. For the first model, independent variables of interest were Repetitive Behavior Scale-Revised subscales: stereotyped behavior, self-injurious behavior, compulsive behavior, ritualistic behavior, sameness behavior, and restricted behavior. For the second model, independent variables of interest were Social Responsiveness Scale, Second Edition subscales: social awareness, social cognitive, social communication, and social motivation. Irritability was significantly associated with several categories of RRBs (i.e., insistence on sameness, stereotypic behavior, and restricted interests/activities). Nonetheless, irritability was not associated with categories of social communication and interaction challenges in autistic youth. Results from this study indicated differing associations between core autism characteristics and affective irritability. Findings highlight the importance of differentiating types of restricted, repetitive behaviors and social communication and interaction challenges in conceptualizing mental health concerns in autistic youth.

Irritability in children: Promising advances in measurement and treatment

Extreme irritability is a challenging quality for children and adolescents and those that live with them; one that often brings them into treatment due to the impact on others. Further, it also leads to a cycle of interpersonal rejection from others based on the unpleasantness of interaction with such an individual. For these reasons, both anger and irritability have received increasing attention from researchers and clinicians in recent years, yet conceptualization is still murky, as is measurement. Is it temperament? Is it a sign of pathology? Specific to mood disorders or a cross‐sectional symptom? Stable and enduring, or not?

Drug-refractory irritability and related factors in autistic children

Objectives Autistic children frequently exhibit irritability, which can manifest as aggression, self-injurious behaviour, and severe tantrums, leading to significant impairments. Two atypical antipsychotics have been licensed by the Food and Drug Administration for the treatment of irritability in autistic children, although a significant percentage of these children do not respond to this treatment. This study aimed to determine the frequency of drug refractory irritability (DRI) and identify the risk factors in a large clinical sample of autistic children. Methods The medical records of 1279 children aged 2–18 years diagnosed with autism and undergoing clinical follow-up were retrospectively analysed. Socioeconomic and clinical characteristics, co-occurring psychiatric disorders and physical conditions were recorded. Results 55% of the sample used antipsychotics to treat irritability, and 8.2% met the DRI criteria. Older age, severe support requirement for autism, language impairment, anxiety disorders, sleep difficulties, gastrointestinal system, and dental problems were found to significantly increase the risk of DRI. Conclusion Our findings indicate that a significant proportion of the clinical sample of autistic children had DRI. The physical, psychiatric, and environmental risk factors identified in our study also highlight heterogeneity in the etiology of DRI. Further research on DRI is needed to develop treatment and prevention strategies.

Effect of Yoga Intervention on Problem Behavior and Motor Coordination in Children with Autism.

Children with autism exhibit more pronounced symptoms of both problem behaviors and motor coordination difficulties. Yoga, recognized as an effective intervention modality, can be valuable after assessing its efficacy in addressing problem behaviors and motor coordination challenges, ultimately contributing to symptom alleviation in autism. The randomized controlled trial (RCT) was used to divide 17 children with autism into an intervention group (n = 9) and a control group (n = 8). The intervention group participated in an 8-week yoga intervention training (three sessions/week, 45-50 min/session), and the control group did not participate in yoga training but only in daily program activities. Pre-test, mid-test, post-test, and after delayed test, teachers assessed the effect of yoga intervention on problem behaviors of children with autism through the Aberrant Behavior Checklist (ABC) and the effect of yoga intervention on motor coordination through the Movement Assessment Battery for Children-Second Edition (MABC2). Results show that the yoga intervention is effective in reducing problem behaviors and improving motor coordination in children with autism. Yoga intervention significantly reduces irritability and social withdrawal in children with autism. Yoga intervention had the most significant improvement in ball skills and static and dynamic balance.

Is irritability multidimensional: Psychometrics of The Irritability and Dysregulation of Emotion Scale (TIDES-13).

Irritability is a common, impairing, and potentially multifaceted manifestation of psychopathology. We designed The Irritability and Dysregulation of Emotion Scale (TIDES-13) to determine whether various expressions of irritability in children and youth form multiple subdimensions with distinct correlates. We administered parent-report (n=3875, mean age=8.9) and youth self-report (n=579, mean age=15.1) versions of TIDES-13 in a population and community-based sample. We conducted exploratory/confirmatory factor analyses and regression analyses to examine the dimensionality of TIDES-13 and the associations of the scale with age, gender, anxiety, depression, ODD, ADHD traits, and the Affective Reactivity Index (ARI). A higher-order model with a global irritability dimension and four subdimensions, including proneness to anger (PA), internalized negative emotional reactivity (iNER), externalized negative emotional reactivity (eNER), and reactive aggression (RA), showed good to excellent fit in both parent-report and self-report. The global irritability dimension showed excellent internal reliability (⍵Total; parent-report=0.97, ⍵Total; self-report=0.95), explained a majority of the item variance (⍵Hierarchical; parent-report=0.94, ⍵Hierarchical; self-report=0.90), and was moderately correlated with the ARI (rparent=0.68, rself=0.77). Subdimensions PA, eNER, and RA were negatively associated with age in males, whereas iNER was positively associated with age in females. Traits of ODD and ADHD were associated primarily with the global irritability dimension, whereas iNER was strongly associated with anxiety and depression traits over and above the global irritability dimension. Our results support a unidimensional interpretation of irritability in a population sample. However, limited evidence of specific behavioral, age, and sex correlates with particular irritability subdimensions may warrant further investigation.

A network approach to the investigation of childhood irritability: probing frustration using social stimuli.

Self-regulation in early childhood develops within a social context. Variations in such development can be attributed to inter-individual behavioral differences, which can be captured both as facets of temperament and across a normal:abnormal dimensional spectrum. With increasing emphasis on irritability as a robust early-life transdiagnostic indicator of broad psychopathological risk, linkage to neural mechanisms is imperative. Currently, there is inconsistency in the identification of neural circuits that underlie irritability in children, especially in social contexts. This study aimed to address this gap by utilizing a functional magnetic resonance imaging (fMRI) paradigm to investigate pediatric anger/frustration using social stimuli. Seventy-three children (M = 6 years, SD = 0.565) were recruited from a larger longitudinal study on irritability development. Caregivers completed questionnaires assessing irritable temperament and clinical symptoms of irritability. Children participated in a frustration task during fMRI scanning that was designed to induce frustration through loss of a desired prize to an animated character. Data were analyzed using both general linear modeling (GLM) and independent components analysis (ICA) and examined from the temperament and clinical perspectives. ICA results uncovered an overarching network structure above and beyond what was revealed by traditional GLM analyses. Results showed that greater temperamental irritability was associated with significantly diminished spatial extent of activation and low-frequency power in a network comprised of the posterior superior temporal sulcus (pSTS) and the precuneus (p < .05, FDR-corrected). However, greater severity along the spectrum of clinical expression of irritability was associated with significantly increased extent and intensity of spatial activation as well as low- and high-frequency neural signal power in the right caudate (p < .05, FDR-corrected). Our findings point to specific neural circuitry underlying pediatric irritability in the context of frustration using social stimuli. Results suggest that a deliberate focus on the construction of network-based neurodevelopmental profiles and social interaction along the normal:abnormal irritability spectrum is warranted to further identify comprehensive transdiagnostic substrates of the irritability.

Irritability as a Transdiagnostic Risk Factor for Functional Impairment in Autistic and Non-autistic Toddlers and Preschoolers.

Trait irritability in toddlerhood is a powerful risk factor for later internalizing and externalizing challenges in non-autistic children, but the predictive clinical utility of irritability is unknown in autism. Irritability is a trait-level emotional response (i.e., frustration) to a blocked goal and is one source of disruptive behavior. Irritability has two facets: Frustration is the degree to which emotion is elevated after a blocked goal, while soothability is the rate of recovery from peak distress. We aimed to: (1) compare and describe the two facets of irritability in non-autistic and young autistic children, and (2) assess whether children's reward sensitivity and executive function moderate the relation between irritability and clinical symptoms. Participants were 90 autistic (n=43) and non-autistic (n = 47) 2- and 4-year-olds. Autistic children did not have different levels of frustration but were more difficult to soothe compared to non-autistic children, according to parents. Further, frustration and soothability were less strongly correlated for autistic compared to non-autistic children. For all children, executive function (specifically, inhibition) moderated, or ameliorated the strength of, the relation between irritability (both soothability and frustration) and externalizing challenges. This study provides evidence for irritability as a transdiagnostic risk factor for clinically significant emotion regulation challenges. Further, the effect of trait irritability may be ameliorated by children's executive function in a transdiagnostic manner. Future work should examine the unique aspects of soothability to how irritability presents within autism, as well as evaluate and modify emotion regulation interventions for autistic toddlers and preschoolers.

Therapeutic Drug Monitoring to Optimize Risperidone Treatment in Children with Autism Spectrum Disorder.

Risperidone is an atypical antipsychotic drug used to treat irritability and aggression in children and adolescents with autism spectrum disorder. In an earlier study, the sum trough concentration of risperidone and its metabolite (9-hydroxyrisperidone) was positively correlated with weight gain and effectiveness. The aim of this study was to determine the therapeutic window for risperidone sum trough concentrations that balances weight gain with treatment effectiveness in this population. In addition, the effect of therapeutic drug monitoring (TDM) on treatment optimization was simulated. In a retrospective cohort (n = 24 children), the target window for risperidone leading to the least increase in body mass index z-scores while retaining effectiveness as measured by the irritability subscale of the Aberrant Behavior Checklist was determined using receiver operating curve analysis. This target range was used to simulate the effect of TDM using a population PK model implemented in the software platform InsightRX. Dosing advice was based on plasma trough concentrations and the dose administered at 12 weeks to simulate whether more children would be on target at 24 weeks after the start of treatment. A risperidone sum trough target range of 3.5-7.0 mcg/L would minimize increase in body mass index z-score and optimize effectiveness. Dosing advice using TDM and a population PK model would lead to a larger proportion of children achieving the target concentration range (62.5% versus 16.7%). TDM may be a useful tool for optimizing risperidone treatment in children and adolescents with autism spectrum disorder.

Characteristic Similarities of Irritability Between Autism and Disruptive Mood Dysregulation Disorder.

Objective: Irritability in children with autism spectrum disorder (ASD) is prominent and often leads to distress to both autistic children and their families. However, the nature of irritability in autism and the difference from nonautistic children have rarely been examined. This study aimed to investigate the clinical characteristics of irritability in autism, and to compare the symptom profiles with those of disruptive mood dysregulation disorder (DMDD) in nonautistic children. Methods: Fifty-six children aged 7-17 years (mean age 10.36 ± 3.05) were recruited into this study (21 with DMDD, 21 with high-functioning autism [hfASD], and 14 healthy volunteers [HV]). Their parents completed the Aberrant Behavior Checklist-Irritability (ABC-I) subscale and the Strengths and Difficulties Questionnaire (SDQ) parent report form. The ABC-I subscale was analyzed as a whole and broken into subsets (ABC-I-Irritability, ABC-I-Agitation, and ABC-I-Crying). The symptom profiles of irritability and the association with psychosocial difficulties were compared between groups. Results: The ABC-I-Irritability scores of children with hfASD closely matched to those of children with DMDD. In addition, both DMDD and hfASD groups could be differentiated from HV group in five of the six items except "depressed mood." However, in the ABC-I-Agitation scale, children with DMDD, but not hfASD, had higher scores in "Aggressive to other patients and staff" and "Stamps feet while banging objects or slamming doors" than HV. Regarding psychosocial outcomes, irritability in children with DMDD and hfASD were associated with emotional problems as measured by the SDQ. Moreover, irritability in DMDD was associated with conduct problems, and the hfASD group exhibited the similar trend. Conclusions: Symptom profiles of irritability and the associated emotional and conduct problems in children with hfASD were similar to those of DMDD in the nonautistic population. Future studies are warranted to explore the underlying neurophysiological mechanisms of irritability between autistic and nonautistic children for further insight into the nature of irritability in autism.

Psychometric Evaluation of the Affective Reactivity Index Among Children and Adolescents in China: A Multi-Method Assessment Approach.

The Affective Reactivity Index (ARI) is one of the most studied scales for assessing youth irritability, but little is known about its measurement performance in community populations. This study applied item response theory (IRT), network analysis, and classical test theory (CTT) to examine the psychometric properties of the ARI in a sample of n = 395 community-based children (Mage = 13.44, SD = 2.51) and n = 403 parents. In this sample, the ARI demonstrated good reliability, as well as convergent and concurrent validity. The one-factor structure was supported by both confirmatory factor analysis (CFA) and network analysis. IRT analysis revealed that the ARI effectively distinguished between various levels of irritability within the community population. Network analysis identified "Loses temper easily,""Gets angry frequently," and "Often loses temper" are central aspects of irritability. The findings support the ARI as a brief, reliable, and valid instrument to assess irritability in community children and adolescents.

3.41 Change Matters: Using Latent Growth Curve Model to Study the Trajectory of Irritability in Children and Youth Throughout the COVID-19 Pandemic

3.41 Change Matters: Using Latent Growth Curve Model to Study the Trajectory of Irritability in Children and Youth Throughout the COVID-19 Pandemic

L -carnitine adjunct to risperidone for treatment of autism spectrum disorder-associated behaviors: a randomized, double-blind clinical trial.

The present study was designed to evaluate the efficacy and safety of l-carnitine as an adjuvant agent to risperidone in the treatment of autism spectrum disorder (ASD)-associated behaviors. In this study, 68 children with confirmed ASD were randomly allocated to receive either l-carnitine (150 mg/day) or matched placebo in addition to risperidone. We utilized the Aberrant Behavior Checklist-Community Edition scale (ABC-C) and a checklist of potential adverse effects to assess changes in behavioral status and safety profile at weeks 0, 5 and 10 of the trial. The primary outcome was defined as a change in the irritability subscale score. Sixty patients with similar baseline characteristics completed the trial period. Although scores of ABC-C subscales significantly decreased in both groups over the trial period, the combination of l-carnitine and risperidone resulted in more reduction on the irritability and hyperactivity subscales compared to the combination of risperidone and placebo ( P = 0.033 and P < 0.001, respectively). However, changes in lethargy, stereotypic behavior and inappropriate speech subscales were similar between groups. In conclusion, l-carnitine adjuvant to risperidone could improve irritability and hyperactivity features in children with ASD. Results of this study should be considered preliminary and further clinical trials with larger sample sizes and longer follow-up periods are warranted.

Future Directions in Youth Irritability Research

ABSTRACT Research on irritability in children and adolescents has proliferated over the last 20 years. The evidence shows the clinical and developmental significance of irritable mood and behavior in youth, and it has led to significant changes in mental health classification, diagnosis, and services. At the same time, this research (including our own) has led to relatively little new in terms of practical, empirically based guidance to improve interventions and outcomes. In this article, we briefly summarize some of these developments and current evidence-based practices. We then put forth two key substantive challenges (the “whats”) for future research to address: (a) the need for more effective treatments, especially evaluating and adapting evidence-based treatments that are already well-established for problems related to irritability (e.g., cognitive-behavioral therapies for internalizing and externalizing problems); and (b) the need for a better mechanistic understanding of irritability’s phenomenology (e.g., phasic vs. tonic irritability, how frustration unfolds) and putative underlying mechanisms (e.g., cognitive control, threat and reward dysfunction). Lastly, we suggest three methodological approaches (the “hows”) that may expedite progress in such areas: (a) ecological momentary assessment, (b) digital health applications, and (c) leveraging existing datasets. We hope this article will be useful for students and early-career researchers interested in tackling some of these important questions to better meet the needs of severely irritable youth.

Sleep disturbances are associated with irritability in ASD children with sensory sensitivities

BackgroundParent reports suggest that 44–84% of children with ASD exhibit sleep disturbances that are of clinical concern. Previous studies have reported that, in children with ASD, the severity of sleep disturbances is associated with the severity of either sensory problems or aberrant behaviors, but none have performed combined analyses with measures of both sensory and aberrant behaviors symptom domains from the same children.MethodsWe examined parent reports of 237 children with ASD, 1.4–8.7 years old, using the child sleep habits questionnaire (CSHQ), sensory profile (SP), and aberrant behaviors checklist (ABC).ResultsThe analyses revealed that sleep disturbances were most strongly associated with SP sensory sensitivity and ABC irritability scores. Together these scores explained 35% of the variance in total CSHQ scores. Moreover, sensory sensitivity scores moderated the association between irritability and sleep disturbances, indicating that sleep disturbances were significantly associated with irritability only in children with moderate to severe sensory sensitivities.ConclusionWe suggest that the three symptom domains may interact and exacerbate each other such that successful intervention in one symptom domain may have positive impact on the others. Further intervention studies testing this hypothesis are highly warranted.

Longitudinal Associations Between COVID-19 Stress and the Mental Health of Children With ADHD

Objective: To investigate the longitudinal associations between COVID-19 induced stress (related to COVID-19 restrictions/changes), attention-deficit/hyperactivity disorder (ADHD) symptoms, oppositional symptoms, and mental health outcomes (negative affect, anxiety, depression, and irritability) in children with ADHD during the COVID-19 pandemic. Method: Parents of 140 Australian children with ADHD (aged 5–17 years) completed an online survey in May 2020 during stay-at-home restrictions and 12-months later. Results: Baseline COVID-19 stress was associated with increased total ADHD symptom severity (β = .21, p = .007) and hyperactivity/impulsivity symptoms (β = .23, p = .002) at 12-months, after accounting for covariates (i.e., child age, gender, ADHD medication, socio-economic status, and baseline symptoms). Despite some indication of associations between baseline COVID-19 stress and 12-month oppositional symptoms and negative affect, these were attenuated when adjusting for baseline symptoms. Conclusions: The study provides initial evidence of the medium-term impacts of pandemic-related stress for children with ADHD.

Longitudinal associations between early childhood irritability and adolescent depression symptoms in autistic children are mediated by peer relationships but not educational engagement.

In the general population, irritability is associated with later depression. Despite irritability being more prevalent in autistic children, the long-term sequelae are not well explored. We tested whether irritability in early childhood predicted depression symptoms in autistic adolescents, and whether associations could be explained by difficulties in peer relationships and lower educational engagement. Analyses tested the longitudinal associations between early childhood irritability (ages 3-5) and adolescent depression symptoms (age 14) in a prospective inception cohort of autistic children (N = 390), followed from early in development shortly after they received a clinical diagnosis. Mediators were measured in mid-childhood (age 10) by a combination of measures, from which latent factors for peer relationships and educational engagement were estimated. Results showed early childhood irritability was positively associated with adolescent depression symptoms, and this association remained when adjusting for baseline depression. A significant indirect pathway through peer relationships was found, which accounted for around 13% of the association between early childhood irritability and adolescent depression, suggesting peer problems may partially mediate the association between irritability and later depression. No mediation effects were found for education engagement. Results highlight the importance of early screening and intervention for co-occurring irritability and peer problems in young autistic children.

The effect of therapeutic drug monitoring of risperidone and aripiprazole on weight gain in children and adolescents: the SPACe 2: STAR (trial) protocol of an international multicentre randomised controlled trial

BackgroundAntipsychotic drugs are an important part of the treatment of irritability and aggression in children with an autism spectrum disorder (ASD). However, significant weight gain and metabolic disturbances are clinically relevant side effects of antipsychotic use in children. In the SPACe study, we showed positive correlations between both risperidone and aripiprazole plasma trough concentrations and weight gain over a 6-month period. The trial SPACe 2: STAR is designed as a follow-up study, in which we aim to research whether therapeutic drug monitoring in clinical practice can prevent severe weight gain, while retaining clinical effectiveness.MethodsSPACe 2: STAR is an international, multicentre, randomised controlled trial (RCT). One hundred forty children aged 6 to 18 who are about to start risperidone or aripiprazole treatment for ASD related behavioural problems will be randomised into one of two groups: a therapeutic drug monitoring (TDM) group, and a care as usual (CAU) group. Participants will be assessed at baseline and 4, 10, 24, and 52 weeks follow-up. In the TDM group, physicians will receive dosing advice based on plasma levels of risperidone and aripiprazole and its metabolites at 4 and 10 weeks. Plasma levels will be measured in dried blood spots (DBS). The primary outcome will be BMI z-score at 24 weeks after start of antipsychotic treatment. Among the secondary outcomes are effectiveness, metabolic laboratory measurements, levels of prolactin, leptin and ghrelin, extrapyramidal side effects, and quality of life.DiscussionThis will be the first RCT evaluating the effect of TDM of antipsychotic drugs in children and adolescents. Thus, findings from SPACe 2: STAR will be of great value in optimising treatment in this vulnerable population.Trial registrationClinicalTrials.gov Identifier: NCT05146245. EudraCT number: 2020–005450-18. Sponsor protocol name: SPACe2STAR. Registered 8 June 2021. Protocol Version 6, Protocol date: 18 august 2022.